Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine
| Autor: | Koichiro E. Kishi, Yoon Seok Kim, Masahiro Fukuda, Masatoshi Inoue, Tsukasa Kusakizako, Peter Y. Wang, Charu Ramakrishnan, Eamon F.X. Byrne, Elina Thadhani, Joseph M. Paggi, Toshiki E. Matsui, Keitaro Yamashita, Takashi Nagata, Masae Konno, Sean Quirin, Maisie Lo, Tyler Benster, Tomoko Uemura, Kehong Liu, Mikihiro Shibata, Norimichi Nomura, So Iwata, Osamu Nureki, Ron O. Dror, Keiichi Inoue, Karl Deisseroth, Hideaki E. Kato |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Models Molecular PLCR pump-like channelrhodopsin Article General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Structure-Activity Relationship channelrhodopsin Channelrhodopsins ChRmine microbial opsin Sf9 Cells Animals Humans optogenetics Phylogeny Schiff Bases Cryoelectron Microscopy Mice Inbred C57BL all-optical HEK293 Cells cryo-EM Female Ion Channel Gating structure-guided engineering |
| Zdroj: | Cell |
| ISSN: | 0092-8674 |
| Popis: | ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.0 Å resolution cryo-EM structure of ChRmine, revealing architectural features atypical for channelrhodopsins: trimeric assembly, a short transmembrane-helix 3, a twisting extracellular-loop 1, large vestibules within the monomer, and an opening at the trimer interface. We applied this structure to design three proteins (rsChRmine and hsChRmine, conferring further red-shifted and high-speed properties, respectively, and frChRmine, combining faster and more red-shifted performance) suitable for fundamental neuroscience opportunities. These results illuminate the conduction and gating of pump-like channelrhodopsins and point the way toward further structure-guided creation of channelrhodopsins for applications across biology. 新規光駆動型イオンチャネルの構造解明と高性能分子ツールの創出 --神経科学に光を当てる--. 京都大学プレスリリース. 2022-02-03. |
| Databáze: | OpenAIRE |
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